Diabetes Glucose Tolerance Research Articles

Biomarkers of Oxidative Stress in Metabolic Syndrome and Associated Diseases.

Metabolic syndrome (MS) represents worldwide public health issue characterized by a set of cardiovascular risk factors including obesity, diabetes, dyslipidemia, hypertension, and impaired glucose tolerance. The link between the MS and the associated diseases is represented by oxidative stress (OS) and by the intracellular redox imbalance, both caused by the persistence of chronic inflammatory conditions that characterize MS. The increase in oxidizing species formation in MS has been accepted as a major underlying mechanism for mitochondrial dysfunction, accumulation of protein and lipid oxidation products, and impairment of the antioxidant systems. These oxidative modifications are recognized as relevant OS biomarkers potentially able to (i) clarify the role of reactive oxygen and nitrogen species in the etiology of the MS, (ii) contribute to the diagnosis/evaluation of the disease's severity, and (iii) evaluate the utility of possible therapeutic strategies based on natural antioxidants. The antioxidant therapies indeed could be able to (i) counteract systemic as well as mitochondrial-derived OS, (ii) enhance the endogenous antioxidant defenses, (iii) alleviate MS symptoms, and (iv) prevent the complications linked to MS-derived cardiovascular diseases. The focus of this review is to summarize the current knowledge about the role of OS in the development of metabolic alterations characterizing MS, with particular regard to the occurrence of OS-correlated biomarkers, as well as to the use of therapeutic strategies based on natural antioxidants.

Hypertriglyceridaemia predicts subsequent long-term risk of cardiovascular events in Chinese adults: 23-year follow-up of the Daqing Diabetes Study.

Limited information is available on the long-term risk of cardiovascular disease (CVD) associated with hypertriglyceridaemia (HTG) in the Chinese population. We estimated this risk over a 23-year period in participants recruited from among those included in the Da Qing Diabetes Study. A total of 833 Chinese adults including 379 with normal glucose levels and 454 with hyperglycaemia were identified by their oral glucose tolerance in 1986 in Da Qing, China. CVD outcomes were monitored until 2009. Thirty-four percent (280/833) of the participants had HTG, which was defined as a fasting plasma triglyceride (TG) level≥1.7mmol/L, at the baseline time point. Over the 23-yearfollow-up period, 149 subjects in the HTG group and 190 subjects in the non-HTG group (NTG group) experienced their first CVD event, including fatal or nonfatal myocardial infarction (MI) and stroke. The age and sex-adjusted annual incidence of the first CVD event per 1000 person-years was 30.23 for the HTG group vs 18.68 for the NTG group. The corresponding rates for MI and stroke were 7.71 vs 3.89 and 19.55 vs 13.98, respectively. After adjusting for confounders, the HTG group had a 28% higher risk of the first CVD event than the NTG group. This association was significant among only the subjects with a serum cholesterol level>5.7mmol/L and those with diabetes or impaired glucose tolerance (IGT). HGT predicted a substantially higher subsequent long-term risk of the first CVD event in Chinese adults, especially in those with hypercholesterolaemia and hyperglycaemia.

Phytochemical analysis and anti-diabetic, anti-inflammatory and antioxidant activities of Loranthus acaciae Zucc. Grown in Saudi Arabia

The Loranthus genus has been demonstrated to be used in the treatment of wide range of diseases e.g. diabetes, inflammations and cancers. Many species of Loranthus represent a major source of biologically active constituents. Therefore, our study was carried out to investigate the anti-diabetic, anti-inflammatory and antioxidant effects of Loranthus acaciae Zucc. (Loranthaceae) grown in Saudi Arabia. Moreover, our research concerned the guided-fractionation and isolation of possible active compounds from this species. The crude ethanolic extract and its n-hexane, chloroform and n-butanol fractions were investigated for antidiabetic activity utilizing two methods namely, in alloxan-induced diabetic rats and glucose tolerance test in normal rats. Additionally, the anti-inflammatory activity was studied by the carrageenan-induced rat paw oedema method while DPPH free radical scavenging and β-carotene bleaching assays were utilized to determine the antioxidant activity. Various chromatographic and spectroscopic techniques were utilized for the isolation and characterization of the active compounds. Our results exhibited that the crude extract and chloroform fraction has the greatest hypoglycemic and antidiabetic effects. The chloroform fraction and crude extract produced at a dose of 500 mg/kg a significant hypoglycemic effect in diabetic rats with 47.0 and 33.6% reduction in blood sugar levels and in normoglycemic rats 35.6 and 35.4% respectively. A potent anti-inflammatory effect (67.2% at 500 mg/kg) was detected for the chloroform fraction. In addition, the chloroform fraction exhibited a high antioxidative and DPPH-radical inhibitory activity (85.4 and 88.3% respectively). The phytochemical analysis of L. acaciae led to the isolation and characterization of four compounds namely, quercetin 3-O-β-D-glucopyranoside (compound 1), quercetin 3-O-β-(6-O-galloyl)-glucopyranoside (compound 2), (-) catechin (compound 3), and catechin 7-O-gallate (compound 4). Among these compounds quercetin 3-O-β-D- glucopyranoside, quercetin 3-O-β-(6-O-galloyl)-glucopyranoside and catechin 7-O-gallate, are isolated for the first time from this plant.

Impact of Nutrient Type and Sequence on Glucose Tolerance: Physiological Insights and Therapeutic Implications.

Pharmacological and dietary interventions targeting postprandial glycemia have proved effective in reducing the risk for type 2 diabetes and its cardiovascular complications. Besides meal composition and size, the timing of macronutrient consumption during a meal has been recently recognized as a key regulator of postprandial glycemia. Emerging evidence suggests that premeal consumption of non-carbohydrate macronutrients (i.e., protein and fat “preloads”) can markedly reduce postprandial glycemia by delaying gastric emptying, enhancing glucose-stimulated insulin release, and decreasing insulin clearance. The same improvement in glucose tolerance is achievable by optimal timing of carbohydrate ingestion during a meal (i.e., carbohydrate-last meal patterns), which minimizes the risk of body weight gain when compared with nutrient preloads. The magnitude of the glucose-lowering effect of preload-based nutritional strategies is greater in type 2 diabetes than healthy subjects, being comparable and additive to current glucose-lowering drugs, and appears sustained over time. This dietary approach has also shown promising results in pathological conditions characterized by postprandial hyperglycemia in which available pharmacological options are limited or not cost-effective, such as type 1 diabetes, gestational diabetes, and impaired glucose tolerance. Therefore, preload-based nutritional strategies, either alone or in combination with pharmacological treatments, may offer a simple, effective, safe, and inexpensive tool for the prevention and management of postprandial hyperglycemia. Here, we survey these novel physiological insights and their therapeutic implications for patients with diabetes mellitus and altered glucose tolerance.

Abstract P203: Lipoprotein Particle Number and Particle Size Profile in Impaired Fasting Glucose or Impaired Glucose Tolerance Are Similar to Those With Diabetes: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Introduction: Although studies have evaluated the association between the lipid profile measured by nuclear magnetic resonance (NMR) and the diagnosis of diabetes, scarce data are available addressing the association of lipoprotein particles and lipoprotein size among people with impaired fasting glucose and impaired glucose tolerance. Hypothesis: People with impaired fasting glucose and impaired glucose tolerance have a more atherogenic lipid profile measured by lipoprotein particle concentration and size compared to subjects without glucose homeostasis alterations and with a similar pattern of to people with diabetes. Methods: We tested this hypothesis among 5060 men and women aged 35 to 74 years-old enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We measured lipids and lipoproteins subfractions using NMR spectroscopy (LabCorp): 5 triglyceride-rich lipoprotein particles (TRL-P, from very large to very small), 3 LDL-P and 3 HDL-P (large, medium, small) subclasses. Diabetes was defined: fasting plasma glucose ≥126 mg/dl, 2h post-load glucose ≥200 mg/ dl, HbA1c ≥6.5 % or treatment for diabetes; impaired fasting glucose as fasting plasma glucose <126 and >110 mg/dl; impaired glucose tolerance as 2h post-load 75g-glucose between 140-199 mg/dl. Pre-diabetes was defined when one condition impaired fasting glucose or impaired glucose tolerance was identified. We used generalized linear regression models adjusted by sociodemographic/cardiovascular risk factors and lipids measured by enzymatic methods to compare the mean values of each lipoprotein variable. Results: Of the 4,095 subjects (mean age 50± 8.7years-old; 53% women), 706 subjects were diagnosed with diabetes, 365 with impaired fasting glucose, 904 with impaired glucose tolerance, and 2,120 had no glucose homeostasis change (reference group for all comparisons). People with pre-diabetes and diabetes had higher levels of large triglyceride-rich particles (P<0.0001 for all). Subjects with diabetes had lower levels of medium TRL-P; and people with diabetes and impaired glucose tolerance had lower levels of small TRL-P (respectively, P<0.0001, P=0.02). All groups had higher levels of both total LDL-P (P<0.0001 for all) small LDL-P (P<0.0001 for all). HDL particles (total and small) were lower only among subjects with diabetes. Compared with the participants without glucose homeostasis change, the participants with diabetes and pre-diabetes had higher TRL-P sizes (P<0.0001 for all), lower HDL-P sizes (P<0.04 for all), but lower LDL-P sizes were observed for persons with diabetes and impaired glucose tolerance. (P<0.009 for all). Conclusions: Our results suggest that people with impaired fasting glucose or impaired glucose tolerance had a proatherogenic profile of lipoprotein particles compared to people with normal glucose homeostasis and similar to subjects with diabetes.

Abstract P116: The Oral Glucose Tolerance Test is Highly Reproducible for the Diagnosis of Diabetes in Africans: The Africans in America Study

Introduction: As the diabetes epidemic spreads across Africa, the oral glucose tolerance test (OGTT) has the potential to provide important information on glucose tolerance category for the individual and across the population. However, for both patient care and the collection of prevalence statistics, there needs to be a high degree of certainty that the diagnosis made by a single OGTT is reproducible. There are no rigorous studies on the reproducibility of the OGTT in Africans. Objective: By performing two OGTT in African-born blacks living in the Washington DC area, our goal was to evaluate the reproducibility of: a) the glucose tolerance category b) time to glucose peak, c) shape of glucose curve, d) glucose concentration at 60 minutes. Methods: The participants were 90 African-born blacks (66% male (59/90), age 40±11y (mean±SD), BMI 27.6±4.6 kg/m 2 ), who self-identified as healthy and were enrolled in the Africans in America cohort. Two OGTT were performed 10±8 days apart. At each OGTT plasma samples were taken at -15, 0, 30, 60, 90 and 120 minutes. Diabetes (DM), prediabetes (pre-DM) and normal glucose tolerance (NGT)was defined by ADA guidelines for glucose. The shape of the glucose curve was characterized as monophasic, biphasic or indeterminate. During the OGTT, glucose at 60 minutes ≥ 155 mg/dL was defined as elevated. The κ-statistic was used to evaluate reproducibility (slight 0.00 to 0.20, fair 0.21 to 0.40; substantial 0.61 to 0.80, excellent 0.81 to 1.0). Results: At OGTT-1, DM, pre-DM and NGT occurred in 26% (23/90), 27% (24/90) and 48% (43/90), resp. At OGTT-2, DM, pre-DM and NGT occurred in 21% (19/90), 28% (25/90) and 51% (46/90) resp. Reproducibility for the diagnosis of glucose tolerance status (NGT, pre-DM, or DM) was just substantial (κ=0.66). However, reproducibility for the diagnosis of diabetes (DM or no DM) was excellent (κ=0.88). Furthermore, no one without DM at OGTT-1 was identified as having DM at OGTT-2. The reproducibility of time to glucose peak was only fair (κ=0.32), but 100% of participants with DM had peak glucose after 30 min. Similarly, the shape of the glucose curve had fair reproducibility (κ=0.21), but no one with DM had a biphasic curve. For elevated 60 min glucose, reproducibility was substantial (κ=0.62) and 96% (22/23) of the participants with DM had elevated glucose at 60 min. Conclusion: When duplicate OGTT were performed in Africans, the diagnosis of DM and the morphology of the glucose curves were highly reproducible.

Abstract P117: Prediction of Undiagnosed Diabetes in Africans is Optimized by Using Fasting Plasma Glucose at a Threshold of 100 mg/dL: The Africans in America Study

Introduction and Objectives: Detecting undiagnosed diabetes is the first step towards addressing the diabetes epidemic in Africa. Although there is little experience with diabetes prediction equations in Africans, the A1C-modified Atherosclerosis Risk in Communities (ARIC) diabetes prediction equation was optimized in African Americans. Therefore, we evaluated (a) the ability of the A1C-modified ARIC prediction equation to detect undiagnosed diabetes in African-born blacks living in the United States and (b) the contribution of each biochemical variable to the effectiveness of the equation. Methods: Participants were 400 self-identified healthy African-born blacks enrolled in the Africans in America study (age 38 ±10 (mean ±SD) years, BMI 27.5 ±4.5, range 18.2-42.4 kg/m 2 ). Glucose tolerance status was diagnosed by glucose criteria for the OGTT. The prediction equation had 9 variables; 5 clinical (age, parent history of diabetes, height, waist circumference, and systolic BP); and 4 biochemical (A1C, fasting plasma glucose (FPG), high density lipoprotein (HDL) and triglycerides (TG)). Area under the receiver operating characteristic curve (AUC-ROC) predicted discrimination and Youden Index identified optimal cut-points. Four models were tested. Model 1 determined the predictive value of the full equation. Model 2 included the clinical variables and 3 of the 4 biochemical variables at a time. Model 3 included the clinical variables and 1 biochemical variable at a time. Model 4 evaluated the independent prediction by each biochemical variable. Results: Diabetes, prediabetes and normal glucose tolerance were detected in 7% (26 of 400), 27% (108 of 400) and 66% (266 of 400), respectively. Model 1 had an AUC-ROC of 0.8. Model 2 with FPG excluded had an AUC-ROC of 0.7. When A1C, HDL or TG were the excluded AUC-ROC increased to >0.8. Model 3 with clinical variables and FPG the AUC-ROC was 0.9. However, when A1C, HDL or TG were included AUC-ROC declined to ≤0.7. In Model 4, FPG as a single predictor had an AUC-ROC of 0.9. In contrast, A1C, HDL or TG as single predictors, all had AUC-ROC ≤0.7. For the prediction of diabetes, the optimal cut-point for FPG was 99 mg/dL (sensitivity 85%, specificity 87%). Conclusions: As the prediction of prevalent diabetes by the entire equation and FPG alone were similar, FPG ≥100 mg/dL in Africans may be a sufficient and cost-effective way forward.

A dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, attenuates cardiac dysfunction after myocardial infarction independently of DPP-4

Dipeptidyl peptidase-4 (DPP-4) inhibitors not only improve impaired glucose tolerance in diabetes, but also have pleiotropic extra-pancreatic effects such as preconditioning effect for myocardial ischemia-reperfusion injury. Here, we investigated the anti-remodeling effects of linagliptin, a DPP-4 inhibitor, by use of DPP-4-deficient rats.After the induction of myocardial infarction (MI), Fischer 344 rats with inactivating mutation of DPP-4 were orally administrated with a DPP-4 inhibitor, linagliptin (5 mg kg−1·day−1), or vehicle in drinking water for 4 weeks. Linagliptin did not affect hemodynamic status, body weight, and infarct size. In echocardiography, linagliptin tended to improve left ventricular (LV) systolic function, and significantly improved LV diastolic function, surprisingly. Interstitial fibrosis in marginal region and macrophage infiltration were significantly lower in the linagliptin group than those in the vehicle group. Fibrosis-related gene expressions, such as collagen I and transforming growth factor-β1 (TGF-β1), and inflammation-related expressions, such as macrophage chemotactic protein 1 and matrix metalloproteinase-2 (MMP-2), were significantly suppressed in marginal area of the linagliptin-treated rats compared with the vehicle rats. The TGF-β1 and MMP-2 protein levels were attenuated by linagliptin in DPP-4-deficient cardiac fibroblasts.Linagliptin can attenuate MI-induced cardiac remodeling via a DPP-4-independent pathway.

Deletion distal to the PAX6 coding region reveals a novel basis for familial cosegregation of aniridia and diabetes mellitus

AimsAnalyze cosegregation of aniridia and diabetes to identify genetic criteria for detection and early treatment of diabetes-susceptible aniridia patients. MethodsWe assessed a two-generation family: three individuals with aniridia, two previously diagnosed as type 2 diabetes. One individual with aniridia, with unknown diabetes status, was evaluated by oral glucose tolerance test. Genetic analysis of aniridia-associated genes was performed on all available family members. Candidate genes were functionally tested by gene silencing in MIN6 pancreatic β-cells. ResultsA 25 year old male with aniridia had a diabetic oral glucose tolerance test despite a normal fasting blood glucose. A 484–630 kb deletion ∼120 kb distal to PAIRED BOX 6 (PAX6) showed dominant cosegregation with aniridia and diabetes in all affected family members. The deleted region contains regulatory elements for PAX6 expression and four additional coding regions. Knockdown of two of the deleted genes (Dnajc24 or Immp1l) with Pax6 impaired glucose-stimulated insulin secretion. ConclusionsWe demonstrate dominant cosegregation of diabetes and aniridia with a deletion distal to PAX6, which is clinically distinct from the mild glucose intolerance previously reported with PAX6 coding mutations. Asymptomatic aniridia individuals appear at risk of diabetes (and its complications) and could benefit from earlier diagnosis and treatment.

Type 2 Diabetes Mellitus, Impaired Glucose Tolerance and Associated Comorbidities in Children During 2002–2013 in Children’s Clinical University Hospital, Latvia

Abstract The world has seen a rise of type 2 diabetes mellitus in children during the last 20 years. It is proposed that this increase is due to unhealthy eating habits, increasing obesity, especially among teenagers, and better diagnostics. The main risks associated with diabetes are microvascular and macrovascular complications, which can lead to early disability and premature death. The aim of our study was to identify children with type 2 diabetes mellitus or impaired glucose tolerance and investigate associated comorbidities at the time of diagnosis in the Children’s Clinical University Hospital in Latvia. A retrospective analysis was performed of all children with type 2 diabetes mellitus or glucose tolerance impairment from 2002 till 2013, who were treated in Children’s Endocrinology Centre. According to inclusion criteria, 57 patients were selected of whom 24 (42%) had type 2 diabetes mellitus and 33 (58%) had impaired glucose tolerance. Body mass index was analysed according to percentile and all patients were found to have excess weight. In children with type 2 diabetes mellitus, all patients had body mass index over the 99th percentile. Arterial hypertension was found in 66.7% and dyslipidemia in 54.2% type 2 diabetes mellitus patients. From all type 2 diabetes mellitus patients, 71% (n = 17) were girls and they had statistically significantly higher total cholesterol (p = 0.02) and low-density lipoprotein (p = 0.003) levels. Considering, that girls with type 2 diabetes mellitus have high cardiovascular risk in adulthood, it is very important not only to achieve normal glucose levels early, but also to treat comorbidities, to reduce further microvascular and macrovascular complication risk.

Rising plasminogen activator inhibitor-1 and hypoadiponectinemia characterize the cardiometabolic biomarker profile of women with recent gestational diabetes

BackgroundGestational diabetes (GDM) and milder gestational impaired glucose tolerance (GIGT) identify women at risk of developing type 2 diabetes and cardiovascular disease later in life. Accordingly, the postpartum years after gestational dysglycemia can provide insight into early events in the natural history of these disorders. We thus sought to prospectively evaluate the relationship between gestational glucose tolerance and emerging cardiometabolic biomarkers [adiponectin, chemerin, retinol-binding protein-4 (RBP-4), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1)] at both 1- and 3-years postpartum in a cohort reflecting the full spectrum of gestational dysglycemia (from normal to GIGT to GDM).MethodsThree-hundred-and-thirty-nine women completed a glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, which identified 4 gestational glucose tolerance groups: GDM (n = 105); GIGT (n = 59); abnormal GCT with normal OGTT (n = 99); and normal GCT with normal OGTT (n = 76). At 1- and 3-years postpartum, the women underwent repeat OGTT with measurement of biomarkers (adiponectin/chemerin/RBP-4/CRP/PAI-1).ResultsSerum adiponectin was lower in women with GDM and GIGT at both 1-year and 3-years (both P ≤ 0.002), whereas chemerin, RBP-4, CRP and PAI-1 showed no differences across the 4 groups. Importantly, the change in PAI-1 between 1- and 3-years progressively increased from the normal GCT group to the abnormal GCT group to GIGT to GDM (P = 0.03). Indeed, both GDM (t = 2.98, P = 0.003) and GIGT (t = 2.14, P = 0.03) independently predicted an increase in PAI-1 from 1- to 3-years postpartum.ConclusionsHypoadiponectinemia and rising PAI-1 over time are early features of the cardiometabolic biomarker profile of women with recent gestational dysglycemia.

Diabetes mellitus and heart failure: insights from a toxic relationship

Diabetes mellitus and heart failure: insights from a toxic relationship

The Influence of Outpatients’ Wait Times and Health Care Professionals’ Communication Behaviors on Treatment Satisfaction and the Intention to Drop Out

We studied influences of perceptions of patients’ wait times and communication behaviors of healthcare professionals on treatment satisfaction and the intention to drop out in diabetes outpatients. A questionnaire was sent to 888 outpatients with diabetes or impaired glucose tolerance who visited our clinic in April 2016. We also measured time spent in clinics. Totally, 759 patients responded to the questionnaire; 717 valid responses were obtained for statistical analyses. In the group with the intention to drop out,” many replied that they felt that “the wait time from physical examination to accounting” was long; this association was significant (P = 0.009, χ2 test). Time spent in clinics was also significantly associated with the “perception of wait time (total).” Communication behaviors of healthcare professionals were also significantly associated with the presence of the intention to drop out. Median scores of the first factor of the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were lower in those who intended to drop out than in those who did not (52 vs. 632 patients); the DTSQ first factor score was significantly associated with the presence of intention to drop out (P < 0.001, Mann-Whitney U test). Receiver operating characteristic curve analysis revealed the DTSQ score as a significant predictor of the presence of intention to drop out (area under the curve = 0.746, P < 0.001), with an optimal cut-off of 22.5 (sensitivity 70.6%, specificity 67.3%). The findings of this study suggest that improved treatment satisfaction may reduce incidences of drop out. Thus, improved wait times and better communication behavior from healthcare professions may improve patient satisfaction and reduce the intention to drop out and possibly the dropout rate. Disclosure S. Sato: None. T. Tosaki: Other Relationship; Self; Eli Lilly and Company, Takeda Development Center Asia, Pte. Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation. C. Oshiro: None. A. Kudara: None. A. Inagaki: None. M. Kondo: None. S. Tsunekawa: None. Y. Kato: Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Sanofi, Takeda Pharmaceutical Company, Eli Lilly Japan. H. Kamiya: Other Relationship; Self; MSD K.K., Ono Pharmaceutical Co., Ltd., Sanofi K.K., AstraZeneca, Astellas Pharma KK, Eli Lilly and Company, Novartis Pharma K.K., Dainippon Sumitomo Pharma Co., Ltd, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd. J. Nakamura: Other Relationship; Self; Astellas Pharma US, Inc., AstraZeneca, Ono Pharmaceutical Co., Ltd., MSD K.K., Kyowa Hakko Kirin Co., Ltd., Kowa Pharmaceuticals America, Inc., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Mitsubishi Tanabe Pharma Corporation, Eli Lilly and Company, Novartis Pharma K.K., Pfizer Inc..

Comparison of Different Methods for Carbohydrate Disorder Detection

Measurement of fasting glucose and prandial glucose, as well as glycated haemoglobin (HbA1c) and oral glucose tolerance test (OGTT) could confirm diabetes or impaired glucose tolerance but they are invasive and time consuming methods. Some new technologies assessing dermal changes in perspiration like EZscan are used for defining carbohydrate state. We compare common methods used for detecting carbohydrate disorders with EZscan methodology assessing their potency to reveal diabetic and prediabetic patients. We studied 124 patients (64 males, 60 females, mean age 43.4±8.9years) with very high risk for diabetes. In these patients we measured HbA1c and performed OGTT and diagnosis diabetes or prediabetes was based on general recommendations. In addition patients underwent EZscan test in which diagnosis is based on measurement of electrochemical skin conductance. Only in 37 patients (29.8%) HbA1c was above 6.5% and in another 38 patients (30.6%) HbA1c was between 6.0-6.49%. After performing OGTT 22 patients (17.7%) were defined with increased fasting glucose (IFG) and 37 patients (29.8%) were with impaired glucose tolerance (IGT), 58 patients (46.7%) were with diabetes. Results from EZscan test show that 65 patients (52.4%) are with IFG/IGT and 55 patients (44.3%) are with diabetes. Age and gender did not have influence on the results. We conclude that EZscan could be used as test with similar to OGTT power for diagnosis of diabetes. HbA1c shows least potency for diagnosis. EZscan presents with some additional advantages being noninvasive method, taking no more than five minutes, with no need of special condition. Disclosure I. Daskalova: None. T. Totomirova: None. N. Petrov: None.

Phenotypic Multiorgan Involvement of Subclinical Disease as Quantified by Magnetic Resonance Imaging in Subjects With Prediabetes, Diabetes, and Normal Glucose Tolerance.

Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls. Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement. Magnetic resonance features were summarized in a phenotypic-based score (range, 0-6). Univariate, multivariate correlation, and unsupervised clustering were performed. Among 243 subjects with complete multiorgan MR data sets included in the analysis (55.6 ± 8.9 years, 62% males), 48 were classified as subjects with prediabetes and 38 as subjects with diabetes. The MR phenotypic score was significantly higher in subjects with prediabetes and diabetes as compared with controls (mean score, 3.00 ± 1.04 and 2.69 ± 0.98 vs 1.22 ± 0.98, P < 0.001 respectively), also after adjustment for potential confounders. We identified 2 clusters of MR phenotype patterns associated with glycemic status (P < 0.001), independent of the MR score (cluster II-metabolic specific: odds ratio, 2.49; 95% CI, 1.00-6.17; P = 0.049). Subjects with prediabetes and diabetes have a significantly higher phenotypic-based score with a distinctive multiorgan phenotypic pattern, which may enable improved disease characterization.

Comparison of health-related quality of Life (HRQOL) among patients with pre-diabetes, diabetes and normal glucose tolerance, using the 15D-HRQOL questionnaire in Greece: the DEPLAN study

BackgroundDiabetes mellitus is usually preceded by a pre-diabetic stage before the clinical presentation of the disease, the influence of which on persons’ quality of life is not adequately elucidated. The purpose of this study was to compare the Health-Related Quality of Life (HRQOL) of persons with pre-diabetes with that of diabetes or normal glucose tolerance (NGT), using the validated HRQOL-15D questionnaire.MethodsThe HRQOL-15D scores of 172 people with pre-diabetes (108 with Impaired Fasting Glucose [IFG], 64 with Impaired Glucose Tolerance [IGT], aged 58.3 ± 10.3 years) and 198 with NGT (aged 54.4 ± 10.1 years) from the Greek part of the DEPLAN study (Diabetes in Europe - Prevention using Lifestyle, Physical Activity and Nutritional Intervention), were compared to 100 diabetes patients’ scores (aged 60.9 ± 12.5 years, diabetes duration 17.0 ± 10.0 years, HbA1c 7.2 ± 1.2%), derived from the outpatient Diabetes Clinic of a University Hospital.ResultsThe diabetes patients’ HRQOL-15D score (0.8605) was significantly lower than the pre-diabetes’ (0.9008) and the controls’ (0.9092) (p < 0.001). There were no differences in the total score between the controls and the group with pre-diabetes. However, examination of individual parameters of the score showed that people with IGT had lower scores compared to the control group, as related to the parameters of “mobility” and “psychological distress”. No differences were found in any component of the HRQOL-15D score between the control group and the IFG group, nor between the two groups with pre-diabetes (IFG vs. IGT).ConclusionsPersons with pre-diabetes had a similar HRQOL score with healthy individuals, and a higher score than persons with diabetes. Specific components of the score, however, were lower in the IGT group compared to the controls. These findings help clarify the issue of HRQOL of persons with pre-diabetes and its possible impact on prevention.

Reducing the Risk of Developing Diabetes.

Reducing the Risk of Developing Diabetes.

Cardiovascular Protection in People With Diabetes.

Cardiovascular Protection in People With Diabetes.

IAPP/amylin and β-cell failure: implication of the risk factors of type 2 diabetes.

In type 2 diabetes (T2D), the most significant pathological change in pancreatic islets is amyloid deposits, of which a major component is islet amyloid polypeptide (IAPP), also called amylin. IAPP is expressed in β-cells and co-secreted with insulin. Together with the inhibitory effects of synthetic human IAPP (hIAPP) on insulin secretion, our studies, using hIAPP transgenic mice, in which glucose-stimulated insulin secretion was moderately reduced without amyloid deposit, and hIAPP gene-transfected β-cell lines, in which insulin secretion was markedly impaired without amyloid, predicted that soluble hIAPP-related molecules would exert cytotoxicity on β-cells. Human IAPP is one of the most aggregation-prone peptides that interact with cell membranes. While it is widely reported that soluble hIAPP oligomers promote cytotoxicity, this is still a hypothesis since the mechanisms are not yet fully defined. Several hIAPP transgenic mouse models did not develop diabetes; however, in models with backgrounds characterized for diabetic phenotypes, β-cell function and glucose tolerance did worsen, compared to those in non-transgenic models with similar backgrounds. Together with these findings, many studies on metabolic and molecular disorders induced by risk factors of T2D suggest that in T2D subjects, toxic IAPP oligomers accumulate in β-cells, impair their function, and reduce mass through disruption of cell membranes, resulting in β-cell failure. IAPP might be central to β-cell failure in T2D. Anti-amyloid aggregation therapeutics will be developed to create treatments with more durable and beneficial effects on β-cell function.

Clinical and genetic features of Charcot-Marie-Tooth disease 2F and hereditary motor neuropathy 2B in Japan.

Mutations in small heat shock protein beta‐1 (HspB1) have been linked to Charcot‐Marie‐Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1‐related disorders.